DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first-inventor-to-file provisions of the AIA .
Status
Claims 1-16 as filed on 17 January 2025 are examined herein.
Examiner’s Notes & Claim Interpretation
Citations to Applicant’s specification are abbreviated herein “Spec.”
Occasionally, “SIN:” may be used as an abbreviation “SEQ ID NO:” herein.
The following examined U.S. Patent applications are members of the family; all issued as patents. All are Continuation applications (not divisionals).
First, the 15/868,676; now U.S. Patent No. 10,703,782 where the claims focus on SEQ ID NO:6 and SEQ ID NO:12. Both identified as chimeric toxins. pp. 11-12; and para. 0038. The initial claims were the approximately the same as the instant claims.
Second, 16/894,459; now U.S. Patent No. 11,702,455 B2 where the claims focus on SEQ ID NO:8. The initial claims were the approximately the same as the instant claims.
Third, 18/319,022; now U.S. Patent No. 12,240,874; where the claims focus on SEQ ID NO:4 which is a chimeric protein. Spec., para. 0030. The initial claims were the approximately the same although they were immediately replaced by amended claims.
All recited SEQ ID NOs in claim 1 are at least 90% sequence identical to SEQ ID NO:2.
Specification
The specification is objected to because it recites it identifies SEQ ID NO:2 as BCW [lower case ‘o’][lower case ‘o’]1 in the fourth line of paragraph 0075. A typographic error where a lower case ‘o’ was substituted for a zero.
Appropriate correction is requested.
Claim Objections
Claims 2, 3, 4, 12, 14 and 16 are objected to because of the following informalities.
Claims 2, 3, 4, 12 and 16 are objected to because "Lepidopteran" should not be italicized in claims 2-4 (once each), 12 (twice) and 16 (thrice) - it is neither a species nor a genus name therefore there is no reason for it to be italicized.
Claim 2 is also objected to because there is no punctuation such as a semicolon at the end of part (a).
Claim 12 is also objected to because there is no pronoun in front of “polypeptide” in the second line of part (a). There is also no pronoun in front of “chemical compound” in the last line of part (a).
Claim 14 is objected to because it the limitation "the polynucleotide sequence of claim 1" in line 1. A "polynucleotide sequence" is information and not a physical structure - however because Applicant's intent is clear.
Further, in contrast to this claim, other dependent claims recite the limitation "the polynucleotide construct of claim 1." Additionally, this limitation conflicts with "said polynucleotide construct" in the last three words of the claim which could be rejected under 35 USC 112(b) for an ambiguous antecedent basis except, again, Applicant's intent was clear.
Claim 14 is also objected to because part (a) ends with "polynucleotide" rather than "polynucleotide construct" or, less preferably - as per the objection above - "polynucleotide sequence."
Claim 16 is also objected to because it begins part (b) with a capital letter. Claim 16 is also objected to because there should be a space after "Domain" and before "II" and "Ill" in part (b).
Appropriate correction is requested.
35 USC § 112(b)-Based Claim Rejections
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 12, 13, and 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 12-13 are rejected because they recite Markush groups of "agents" without defining the terms. Some of the agents have accepted meanings in the art - e.g. Cry1A and the rest of the Cry proteins. Others, however, do not. For example, "ET35," "ET33," “ET70” and the “TIC” series do not appear to have general art-accepted meanings. They also are not defined in the specification.
The claim also recites “chemical compound” but that genus is vast and unknowable.
Since the identity of the all the agents being referenced cannot be determined, the metes and bounds of the claims cannot be determined.
Furthermore, the meaning of some of these terms could arbitrarily change to designate something different during the lifetime of a patent. Thus, an artisan's ability to determine the metes and bounds of the claim would be impaired. See In re Hammack, 427 F .2d 1378, 1382; 166 USPQ 204, 208 (CCPA 1970).
Claim 15 is rejected because it recites Markush groups of transgenic events without defining the terms. Some of the events can be identified in different patent publications and therefore arguably have accepted meanings in the art. For example, many of the maize events are listed in US Patent Publication 2018/0220656 A1, Gockel et al., assigned to BASF SE. Many of the soybean events are listed in WO2015/144652 A2, Decor et al. assigned to Bayer Cropscience Ag. However, the meaning of others appear to be unknown in the art. For example, the meaning of "T14" appears to be without an art-accepted meaning and is thus indefinite.
Since the identity of some of the lines being referenced is indefinite, the metes and bounds of the claims cannot be determined.
Claim 16 is rejected because it recites the limitation "BCW 001" and uses is in such a fashion that knowing its meaning is required to understand the scope of the claim. The meaning of "BCW 001" is uncertain and creates ambiguity in the claim and thus renders the claim indefinite.
Although the term "BCW" has an art-accepted meaning, black cutworm, the term "BCW 001" does not and Applicant does not explicitly define the term in the specification although Applicant discusses a "BCW protein" in paragraph 0046. In that paragraph BCW 001 is associated with SEQ ID NO:1, but that is not necessarily an exclusive definition and can be reasonably interpreted as exemplary. At the end of line 2 is also includes derivatives.
Since the identity of the protein being referenced is indefinite, the metes and bounds of the claims cannot be determined.
And again, as per In re Hammack referenced above, the meaning of the term can change.
35 USC § 112(a) based Claim Rejections; Written Description
The following is a quotation of 35 U.S.C. 112(a):
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 3-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention as broadly as claimed.
Claim 1 is broadly drawn to an insecticidal protein comprising amino acids 1-607 of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10 or SEQ ID NO:12, on an insecticidal fragment thereof.
Part (b) reads on a fragment having at least 95% identity to a species of part (a); no minimum length is recited for the insecticidal fragment.
Part (c) reads on a fragment having at least 84% identity to a species of part (a).
Part (d) reads on a fragment having at least 64% identity to a species of part (a).
Part (e) reads on amino acids #7 through #607 of one of the aforementioned SEQ ID NOs.
Additionally, the encoding nucleotide sequence is linked to a heterologous promoter.
Claims 3 and 4 depend from claim 1 and recite various insect species where the
claimed protein displays activity.
Dependent claim 5 reads on a vector comprising the polynucleotide construct of claim 1.
Dependent claims 6-7 read on host cells comprising the polynucleotide construct of claim 1.
Dependent claim 8 reads on a plant comprising the polynucleotide construct of claim 1.
Dependent claim 9 reads on a seed; dependent claim 10 reads of various plant parts; and dependent claim 11 reads on any biological sample; all with the construct.
Dependent claim 14 is a method of producing a seed.
Dependent claim 15 requires that the plant of claim 8 has various other transgenic events, such as MON89788.
Independent claim 2 recites 3 specific embodiments of protein toxins and is not rejected under the written description requirement.
Dependent claim 12 reads on composition from claim 2 with an additional agent.
Dependent claim 13 reads on composition from claim 12 with an additional a second additional agent but drawn from a narrower list.
Claims 12 and 13 are rejected under 35 USC 112(b) and thus read on indeterminate genera.
Independent claim 16 is drawn to a protein toxin that has a fragment of SEQ ID NO:2 and a fragment of a Cry1A protein. The claim is rejected under 35 USC 112(b) which arguably or potentially expands the genus.
The pending claims read on the following genera.
Claim 1 reads on a broad genus of toxic peptides in parts (b), (c), and (d). Each of these parts read on proteins that share a reduced level of sequence identity to the protein of part (a). Given that part (a)'s protein also includes fragments of the recited sequences, each of part (b), (c) and (d) read on vast genera of proteins.
In claim 16, first, no minimum length for Domain I is required and second, (a) the limitation 'BCW 001 Domain II - Domain Ill' does not have an art-accepted meaning (see rejection under 35 USC 112(b) supra) and (b) whatever its meaning is, again, no minimum length is required. Therefore claim 16 can be reasonably interpreted as reading on virtually any protein that is toxic towards one of the recited Lepidopteran species.
The Federal Circuit held that a written description of an invention "’requires a precise definition, such as by structure, formula [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials." Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1405 (Fed. Cir. 1997) (quoting Fiers v. Revel, 984 F.2d 1164, 1171, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993)). The court also stated "naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of is not a description of that material." Id., 119 F.3d at 1568, 43 USPQ2d at 1406. The court held that “[a] description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNAs, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus.” Id., 119 F. 3d at 1569, 43 USPQ2d at 1406.
Applicant describes BCW 001, BCW 002, and BCW 003 as protein toxins. Spec., para. 0007. None of these terms have acquired a generally accepted meaning in the art and Applicant does not provide them with explicit definitions.
Figure 1 shows a list of Lepidopteran pest species tested in bioassays with the toxin proteins of the invention. Id., para. 0025. An alignment of BCW 001 / SEQ ID NO:2; BCW 002 / SEQ ID NO:4 and BCW 003 / SEQ ID NO:6 is provided in Figure 2.
SEQ ID NO:2 is a toxin sequence from Bt strain EG4384 designated as BCW 001; SEQ ID NO:8 is identical to SEQ ID NO:2.
SEQ ID NO:4 and SEQ ID NO:10 are chimeric proteins, designated BCW 002, comprising a Cry1Ac domain 1 linked to domains II and Ill of BSW 001 (amino acid #258 - #606) linked to a Cry1Ac protoxin domain at amino acids 608-1177 where the chimeric protein's sequence is described in SEQ ID NO:4. SEQ ID NO:6 differs only from SEQ ID NO:4 at a single amino acid, position 259 near the amino end of the BSW 001 sequence. SEQ ID NO:6 and SEQ ID NO:12 are BCW 003.
In paragraph 0042, Applicant describes that
BCW 001 was discovered as an open reading frame predicting an amino acid sequence having characteristics of a Cry1lA type protein after sequencing the genome of Bacillus thuringiensis strain EG4384. The BCW 001 open reading frame (ORF) encoded a protein of 1180 amino acids and the protein was predicted to have many of the characteristics of Cry1 protein toxins, including an identifiable domain I, II, and III structure, and a characteristic Cry 1 A type protoxin domain at the carboxy terminal half of the predicted protein. The predicted Domain I amino acid sequence (residues 1 through about 258 of SEQ ID NO:2) exhibits about 67% identity to Cry1Ac protein toxin domain I. The predicted Domain II amino acid sequence (residues from about 259 through about residue 459 as set forth in SEQ ID NO:2) exhibits perfect ( 100%) identity to a Cry1Ai2 Domain II. The predicted Domain III amino acid sequence (residues from about 260 through about 606 as set forth in SEQ ID NO:2) exhibits about 63% identity to the corresponding Domain III residues in Cry1Ah2. The pro toxin domain structure of the BCW 00 l predicted protein (about residues 607 through 1180 as set forth in SEQ ID NO:2) exhibits about 96% identity to the corresponding residues in Cry1Aa9. Overall this predicted full length protein exhibits about 83% amino acid sequence identity to a Cry1Ai, and the predicted toxin region from amino acid positions l through about residue 607 as set forth in SEQ ID NO:2 exhibits 76% identity to a Cry1Ai1. It is difficult to assign this new toxin protein to a particular Cry1A class and so the Bacillus thuringiensis nomenclature committee will be provided with this sequence and will establish whether this protein merits its own separate and novel class.
(OCRed from Spec.)
Applicant urges that this might be a new class. Id. Applicant tested SEQ ID NO:2 against pests and found that its activity against BCW was distinguishable from the above-mentioned Cry1Aa, Cry1Ah, and/or Cry1Ai toxin proteins known in the art. Id., para. 0043. SEQ ID NO:2 also demonstrated activity against several other pests. Id., para. 0044.
Applicant describes identifying a Bt strain. Spec., para. 0097.
Applicant identifies SEQ ID NO:2 as the “BCW 001” protein encoded by the isolated gene SEQ ID NO:1. Id. The protein is 1180 amino acids long and is Cry1a-like and has three domains. Id.
In paragraph 0099 Applicant describes creating a chimeric toxin using Cry1Ac but swapping Domain II and Domain III from BCW 001. The sequence of this is SEQ ID NO:4.
Applicant compares SEQ ID NO:4 to other Cry proteins. Fig. 2.
Applicant describes BCW 001, BCW 002, and BCW 003 as protein toxins. Spec., para. 0007.
In Example 2, Applicant describes that BCW 001, BCW 002, and BCW 003 show insecticidal activity especially against Black Cutworm. Spec. para. 0101.
Figure 1 shows a list of Lepidopteran pest species tested in bioassays with the toxin proteins of the invention. Id., para. 0025. An alignment of BCW 001 / SEQ ID NO:2; BCW 002 / SEQ ID NO:4 and BCW 003 / SEQ ID NO:6 is provided in Figure 2.
See also paragraph 0056.
In paragraph 0098, Applicant summarizes sequence identities in Domains I, II and Ill compared to Cry1 A toxins. Domain 1 is 1 through 258. Domain II is 58 through 460. Domain III is 460 to 607. Each domain is characterized as having arguably low sequence identity.
The fragment of 1 to 607 is recited in claim 1.
Applicant describes creating a chimeric polypeptide by linking instant Domains II & Ill into a Cry1Ac protein, resulting in both SEQ ID NO:4 and SEQ ID NO:6. Again, results are shown in Figure 1 - but as far as was tested, all three proteins show the same activity.
In Example 3, Applicant also describes creating chimeric proteins placing instant Domains II & Ill into Cry1 Ab and Cry1 Ca. Spec., pp. 30-31. Applicant also describes creating a chimeric protein using the Domain Ill from Cry1Ca into SEQ ID NO:2. Id. Applicant summarizes the results. Id.
In Example 5, Applicant describes creating plant expression vectors by, e.g. optimizing the encoding sequences for plant expression. Id., pp. 31-34. Results for transgenic maize and sugarcane plants are described. Id.
SEQ ID NO:2's polypeptide is not characterized in the art. In fact, Applicant suggests that it might be a novel class of Cry protein. Spec., para. 0042.
Given that Applicant classifies it as a Cry1 protein (Spec., para. 0097), and that it shares a significant amount of sequence identity with Cry proteins, it is reasonable to draw from the delta-endotoxin art and/or the protein art in general to interpret the scope of the claims regarding the written description requirement.
For example, each delta-endotoxin only has activity against one or few insect species. de Maagd et al. (1999) Appl Environ Microbial 65:4369-74, 4369 (col. 1, para. 1 ). Conservative substitutions in non-conserved regions can have unexpected effects on protein function. Id., Figs. 2 & 3. Even a single amino acid substitution in a delta-endotoxin may alter its insecticidal specificity, and toxicity must be determined empirically. Tounsi et al. (2003) J Appl Microbial 95:23-28, 27. For example, a conservative substitution of a lysine for an arginine in a Cry11 A protein eliminated toxicity to A. aegyptii. Angsuthanasombat et al. (2001) J Biochem Mol Biol 34:402-07, 405 (para. spanning cols. 1-2).
Also, in paragraph 0104, Applicant describes the complexities of Cry1 protein sequences and toxicity to different insect species.
Additionally, the protein art in general describes that while proteins are fairly tolerant to mutations resulting in single amino acid changes, increasing the number of substitutions additively increases the probability that the protein will be inactivated. E.g., Guo et al. (2004) Proc Natl Acad Sci USA 101:9205-10, 9209 (rt. col., para. 2).
Given the broad scope of claim 1, part (d), requiring only 64% sequence identity to a fragment of, e.g., SEQ ID NO:2, the teachings of Guo et al. suggest that changing that many amino acids relative to, e.g. SEQ ID NO:2, has a high likelihood of inactivating the protein.
Further, in the delta-endotoxin art there are known to be extensive functional interactions between the three domains of delta-endotoxins, and it is known that more than one domain is involved in toxin specificity and binding. Aronson & Shai (2001) FEMS Microbial Lett 195:1-8, 7 (para. spanning cols. 1-2). Domains II and Ill are involved in insect specificity (de Maagd et al. (2001) Trends Genet 17:193-99, 194 (col. 2, para. 3)), and Domains I and II have co-evolved towards certain specificities. Id., p. 196 (col. 1, para. 2) & p. 197 (col. 1, para. 4). de Maagd et al concludes that the determination of insect specificity of endotoxins is still not understood. Id., p. 198 (col. 2, para. 2).
In summary, in contrast to the scope of the claimed genus of polypeptide variants, Applicant only describes the sequences in the application. Even though many of these sequences show sequence similarity, they are not a representative number in comparison to the size of the genera claimed. Furthermore, as illustrated above, claim 16 encompasses an even larger genus.
Instead of a representative number of species, however, Applicant may also satisfy the written description requirement by describing structural features that are necessary and/or sufficient for the claimed invention. In Univ. Calif. v. Lilly, the Federal Circuit discussed the application of the written description requirement to inventions in the field of biotechnology. The court held that "[a] description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNAs, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus." Univ. Calif. v. Lilly, 119 F. 3d at 1569, 43 USPQ2d at 1406 (Fed. Cir. 1997).
Applicant provides some description of structure/ function relationships in, for example, the analysis of the chimeric proteins in Example 3 (Spec. paras. 0102-04), but fails to extend this description to the amino acid sequence level yet the claims are drawn to amino acid sequence variants.
The instant specification fails to adequately describe the full extent of the claimed genera. Applicant has not described a representative number polypeptides falling within the claims, nor has the specification fully described structures necessary and/or sufficient for activity in the instant invention to allow one skilled the art to envision the claimed genera, and thus the specification fails to provide an adequate written description of the claimed invention.
Given the lack of written description in the specification, one of skill in the art would not recognize that Applicant was in possession of the genera as broadly as claimed.
Dependent claims are included in this rejection because none provide limitations obviating this rejection.
35 USC § 112(a) based Claim Rejections; Enablement
Claim 15 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The invention features novel plants, e.g. a maize plant containing event DKB89614-9. Each event recited in claim 15 appears to be a separate maize line. Since the plant is essential to the claimed invention it must be obtainable by a repeatable method set forth in the specification or otherwise be readily available to the public. If the plant is not so obtainable or available, the requirements of 35 USC§ 112 may be satisfied by a deposit of the seeds. A deposit of 625 seeds of each of the claimed embodiments is considered sufficient to ensure public availability.
The specification does not disclose a repeatable process to obtain the plant and thus it is not apparent if the plant is readily available to the public.
(a) If a deposit is made under the terms of the Budapest Treaty, then a statement, affidavit or declaration by Applicant, or a statement by an attorney of record over his or her signature and registration number, or someone empowered to make such a statement, stating that the instant invention will be irrevocably and without restriction released to the public upon the issuance of a patent, would satisfy the deposit requirement made herein.
(b) If a deposit has not been made under the Budapest Treaty, then in order to certify that the deposit meets the criteria set forth in 37 CFR 1.801-1.809 and MPEP 2402-2411.05, Applicant may provide assurance of compliance by statement, affidavit or declaration, or by someone empowered to make the same, or by a statement by an attorney of record over his or her signature and registration number showing that:(i) during the pendency of this application, access to the invention will be afforded to the Commissioner upon request;
(ii) all restrictions upon availability to the public will be irrevocably removed upon granting of the patent in accordance with 37 CFR § 1.808(a)(2);
(iii) the deposit will be maintained in a public depository for a period of 30 years or 5 years after the last request or for the effective life of the patent, whichever is longer;
(iv) a test of the viability of the biological material at the time of deposit (see 37 CFR § 1.807); and
(v) the deposit will be replaced if it should ever become inviable.
In addition, the identifying information set forth in 37 CFR 1.809(d) should be added to the specification, if not already present. See 37 CFR 1.801 - 1.809 (MPEP §§ 2401-2411) for additional explanation of these requirements.
Applicant has not deposited any seeds. To perfect the deposit, the deposit must be accepted under the Budapest Treaty or the results of a viability test must be provided.
Additionally, a statement, affidavit of declaration by Applicant, or a statement by an attorney of record over his or her signature and registration number, or someone empowered to make such a statement, stating that the instant invention will be irrevocably and without restriction released to the public upon issuance of a patent is also required.
Claims 1 and 3-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for use of the specific SEQ ID NOs recited in claim 1 part (a), does not reasonably provide enablement for the genus of related proteins as broadly as claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The Federal Circuit in In re Wands lists eight considerations for determining whether or not undue experimentation would be necessary to practice an invention. In re Wands, 858 F2d 731, 8 USPQ2d 1400, 1406 (Fed. Cir. 1988). These factors are: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples of the invention, the nature of the invention, the state of the prior art, the relative skill of those in the art, the predictability or unpredictability of the art, and the breadth of the claims. Id.
For example, , claim 1 reads on a broad genus of toxic peptides in parts (b), (c), and (d). Each of these parts read on proteins that share a reduced level of sequence identity to the protein of part (a).
Continuing, the scope of the claims is discussed supra in the written description rejection. That discussion is incorporated by reference here. Additionally, several claims are rejected under 35 USC 112(b).
Applicant’s teachings are also set forth in the written description rejection and that discussion is also incorporated by reference here,
Again, given the significant amount of sequence identity with Cry proteins, it is reasonable to draw from the teachings in delta-endotoxin art and/or the protein art in general to interpret the scope of the claims regarding whether they are fully enabled compared to their scope.
The discussion of de Maagd et al. (1999) Appl Environ Microbial 65:4369-74, 4369 (col. 1, para. 1 ); Tounsi et al. (2003) J Appl Microbial 95:23-28, 27; Angsuthanasombat et al. (2001) J Biochem Mol Biol 34:402-07, 405 (para. spanning cols. 1-2); and de Maagd et al. (2001) Trends Genet 17:193-99, 196 (col. 1, para. 2, & p. 197, col. 1, para. 4) is also incorporated by reference here.
Thus, Cry proteins are known in the art to have different specificities controlled by their amino acid sequence. SEQ ID NO:2 is asserted to be a new class of Cry1A protein. Spec., 0042. Applicant confirms that the components of SEQ ID NO:2 influence insect specificities in the study of chimeric proteins in Example 3. Spec., paras. 0102-04. But other than this study, Applicant fails to provide guidance for the how the sequence of, e.g. SEQ ID NO:2, can be changed and still retain activity against, e.g. BCW. Applicant also fails to teach which fragments of which chimeric proteins will retain activity against, e.g. BCW.
Claims 1 and 16, for example, read on a vast number of proteins, such as, in the case of part (d), sharing as little as 64% sequence identity with, e.g. SEQ ID NO:2.
Applicant, however, provide no affirmative guidance as to which variant sequences in this universe of possible sequences, or fragments will provide a functional insecticidal polypeptide in the instant invention and which will not.
The claimed invention is not enabled though its claimed scope because the effect of expressing in a plant a heterologous nucleic acid sequence encoding a variant of, e.g. SEQ ID NO:2, or using such a protein to control insect pests, is unpredictable. The effect is unpredictable because, for example, polypeptides that are related to SEQ ID NO:2 do not predictably have insecticidal activity against specific insects because, in part, SEQ ID NO:2 itself was not well characterized in the art at the time of filing the instant application. Additionally, the effect of making widespread amino acid changes to the polypeptide's sequence is unpredictable.
One of skill in the art, after reading the specification, would be uncertain as to both how to make and how to use variants of the recited SEQ ID NOs in, e.g., claim 1 function within the instant invention. One of skill in the art would find it difficult to predict which of the claimed variants could be used in the instant invention, and which could not. Further, as set forth above, the scope of claim 16 is larger still. Although testing individual proteins might be routine, Applicant has provided minimal guidance as to how to proceed.
Regarding claim 2, there is no guidance in either the specification or the art that a protein with three concatenated Domain II/ Domain Ill structures would be functional in the instant invention.
Given the claim breadth regarding variant sequences, combined with the unpredictability in the art, and lack of guidance as discussed above, undue experimentation is required to practice Applicant's invention. Therefore one skilled in the art would be forced to make and test numerous variants of the SEQ ID NOs recited in claim 1 with no guidance as to which ones could be used in the instant invention. Thus Applicant's claimed invention would require undue trial and error experimentation with no reasonable expectation of success. Therefore the invention is not enabled throughout the broad scope of the claims.
Furthermore, regarding claim 1, parts (b), (c) and (d) are not required to have any insecticidal activity, in contrast to parts (a) and (e). By not requiring any activity associated with sequence variants, it is unclear what value an ordinary artisan would derive from making the variants. Therefore Applicant fails to teach how to use the amino acid sequence variants recited in parts (b), (c) and (d).
Dependent claims are included in this rejection because none provide further limitations obviating this rejection.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 2 and 16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claim reads on a first peptide segment comprising a Cry1A Domain I amino acid sequence and a second peptide segment comprising a BCW 001 Domain II - Domain Ill amino acid sequence.
This judicial exception is not integrated into a practical application because it merely reads on a naturally-occurring protein. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because of the following reasons.
Claim 16 is rejected supra under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite because it recites the limitation "BCW 001" where the meaning of "BCW 001" is indefinite. However, "BCW 001" can be reasonably interpreted broadly as follows.
Although Applicant discusses a "BCW protein" in paragraph 0046, by using the term "derived from" at in line 2, Applicant creates an open-ended definition that could be applied to any protein. Applicant teaches that the Domain Ill from a Cry1A protein is 63% identical between the Applicant's SEQ ID NO:2. Thus, a BCW 001 Domain II - Domain Ill amino acid sequence could be "derived from" Cry1A and thus the claim reads on a Cry1 A protein as found in nature. Cry1 A proteins are known to be naturally occurring Bt proteins that are active against, inter alia, 0 nubilalis.
E.g., Malvar & Gilmer, US 7,250,501 B2, Table 5, col. 45.
Furthermore the claim does not even require an isolated protein. Thus, the claimed invention is directed to a naturally-occurring protein that is not patent-eligible pursuant to the Supreme Court decision in Ass'n for Molecular Pathology v. Myriad Genetics, Inc., 133 set 2017, 106 USPO2d 1972 (2013).
Claim 2 is included because, as seen in the alignment below, the recited fragment of SEQ ID NO:2 is identified as a Bt protein (TIC2365). Bayer Crop Sci (2023) TIC2365 GenBank WOH21587.1.
insecticidal protein TIC2365 [Bacillus thuringiensis]
Sequence ID: WOH21587.1Length: 1180Number of Matches: 1
Range 1: 256 to 606GenPeptGraphicsNext MatchPrevious Match
Alignment statistics for match #1
Score Expect Method Identities Positives Gaps
717 bits(1851) 0.0 Compositional matrix adjust. 351/351(100%) 351/351(100%) 0/351(0%)
Query 1 IRTVSQLTREIYTNPVLENFDGSFRGMAQRIEQNIRQPHLMDILNSITIYTDVHRGFNYW 60
IRTVSQLTREIYTNPVLENFDGSFRGMAQRIEQNIRQPHLMDILNSITIYTDVHRGFNYW
Sbjct 256 IRTVSQLTREIYTNPVLENFDGSFRGMAQRIEQNIRQPHLMDILNSITIYTDVHRGFNYW 315
Query 61 SGHQITASPVGFSGPEFAFPLFGNAGNAAPPVLVSLTGLGIFRTLSSPLYRRIILGSGPN 120
SGHQITASPVGFSGPEFAFPLFGNAGNAAPPVLVSLTGLGIFRTLSSPLYRRIILGSGPN
Sbjct 316 SGHQITASPVGFSGPEFAFPLFGNAGNAAPPVLVSLTGLGIFRTLSSPLYRRIILGSGPN 375
Query 121 NQELFVLDGTEFSFASLTTNLPSTIYRQRGTVDSLDVIPPQDNSVPPRAGFSHRLSHVTM 180
NQELFVLDGTEFSFASLTTNLPSTIYRQRGTVDSLDVIPPQDNSVPPRAGFSHRLSHVTM
Sbjct 376 NQELFVLDGTEFSFASLTTNLPSTIYRQRGTVDSLDVIPPQDNSVPPRAGFSHRLSHVTM 435
Query 181 LSQAAGAVYTLRAPTFSWQHRSATTTNIIAADSITQIPAVKGRSIINNGTVISGPGFTGG 240
LSQAAGAVYTLRAPTFSWQHRSATTTNIIAADSITQIPAVKGRSIINNGTVISGPGFTGG
Sbjct 436 LSQAAGAVYTLRAPTFSWQHRSATTTNIIAADSITQIPAVKGRSIINNGTVISGPGFTGG 495
Query 241 DLVRLYNADFNINNRAYLEVPIFFQSPSTNYRVRVRYASTSSLPVDVVFGNISHPTTFPA 300
DLVRLYNADFNINNRAYLEVPIFFQSPSTNYRVRVRYASTSSLPVDVVFGNISHPTTFPA
Sbjct 496 DLVRLYNADFNINNRAYLEVPIFFQSPSTNYRVRVRYASTSSLPVDVVFGNISHPTTFPA 555
Query 301 TARSLDNLQSNDFGYIDIAGTFLPSLGPSIGIRPMLSTINLIVDRFEFIPV 351
TARSLDNLQSNDFGYIDIAGTFLPSLGPSIGIRPMLSTINLIVDRFEFIPV
Sbjct 556 TARSLDNLQSNDFGYIDIAGTFLPSLGPSIGIRPMLSTINLIVDRFEFIPV 606
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless -
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claim 16 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Malvar & Gilmer, US 7,250,501 B2, issued 31 July 2007.
Claim 16 is rejected supra under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite because it recites the limitation "BCW 001" where the meaning of "BCW 001" is indefinite. However, "BCW 001" can be reasonably interpreted broadly as follows.
Although Applicant discusses a "BCW protein" in paragraph 0046, by using the term "derived from" at the beginning of line 3, Applicant creates an open-ended definition that could be applied to any protein.
Applicant teaches that the Domain Ill from a Cry1 A protein is 63% identical between the Applicant's SEQ ID NO:2. Thus, a BCW 001 Domain II - Domain Ill amino acid sequence could be "derived from" Cry1 A and thus the claim reads on a Cry1A protein as found in nature. Cry1A proteins are known to be naturally occurring Bt proteins that are active against, inter alia, 0 nubilalis. E.g., Malvar & Gilmer, US 7,250,501 B2, Table 5, col. 45.
Furthermore the claim does not even require an isolated protein. Therefore Malvar & Gilmer anticipates claim 16.
An alternate broad and reasonable interpretation is that "comprising a Cry1A Domain I amino acid sequence" does not require a full-length Cry1 A Domain I sequence and "comprising a BCW 001 Domain II - Domain Ill amino acid sequence" similarly does not require a full-length sequence. Since neither has a minimum length and both use the open "comprising" language, the claim is reasonably interpreted to read on virtually any Bt protein that displayed the required activity.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
§ 103. Conditions for patentability; non-obvious subject matter
A patent for a claimed invention may not be obtained, .... if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 3-11, 14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (2014) AIW52617.1 in view of Malvar & Gilmer ("MaG"), US 7,250,501 B2, issued 31 July 2007.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
a. Determining the scope and contents of the prior art.
b. Ascertaining the differences between the prior art and the claims at issue.
c. Resolving the level of ordinary skill in the pertinent art.
d. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 1 part (a) recites six amino acid SEQ ID NOs including SEQ ID NO:2. Part (a) also reads on insecticidal fragments of the six SEQ ID NOs. Applicant's specification does not explicitly define "insecticidal fragment" but does define "insecticidal" in paragraph 0052. On page 18, Applicant discusses fragments of SEQ ID NO:2, SEQ ID NO:4 and SEQ ID NO:6
The insect inhibitory BCW 001 toxic fragments can also comprise segments with at least 30, 35, 38, 40, 45, 50, 100, 150, 200, 500, 550, 555, 560, 565, 570, 572, 574, 580 or 585 amino acid residues of the 591 amino acid region corresponding to about residues 28 to about 618 of the sequences of any one of SEQ ID NOs:2, 4, or 6. Spec., para. 0068.
As seen in the alignment below, one of the many Cry1 Aa polypeptides known to the art shares a high degree of sequence identity with instant SEQ ID NO:2. When a fragment that is from approximately residues 130 to 460 from SEQ ID NO:2 is aligned with the Cry protein below, the two are 98% sequence identical. Under the definitions discussed above, a fragment of Yu et al.'s Cry1A protein falls within the scope of part (b) of claim 1.
Malvar & Gilmer teaches using a Cry protein for insect control and while doing so, creates recombinant vectors using heterologous promoters to express a Cry protein. Malvar & Gilmer, col. 17.
Yu et al., being a GenBank entry does not teach the use of its Cry protein. However, it would have been prima facie obvious to one of ordinary skill in the art as of the effective filing date of the claimed invention to express the Cry protein taught by Yu et al. in a polynucleotide construct using a heterologous promoter. Given the level of skill in the art as of the effective filing date of the claimed invention, one of ordinary skill in the art would have had a reasonable expectation of success. Therefore instant claim 1 is obvious. Claim 5, drawn to a vector, is also obvious.
Malvar & Gilmer teaches that their Cry protein is toxic to 0. nubilalis (col. 45, Table 1 ). It is unknown if the Cry protein of Yu et al. is also toxic to 0. nubilalis, or one of the species listed in claim 3 for example, but the toxicity of Yu et al.'s Cry protein is an intrinsic property of the protein, based on the knowledge of the art (e.g. as set forth in the rejections under 35 USC 112(a) supra).
In 2009, the Federal Circuit addressed the question whether a previously undiscovered property of a composition that was otherwise obvious provides a patentable distinction? The Federal Circuit held that it did not, stating that "[e]ven if no prior art of record explicitly discusses the [limitation], the ... application itself instructs that [the limitation] is not an additional requirement imposed by the claims on the [claimed invention], but rather a property necessarily present in the [claimed invention]."
In re Kubin, 561 F.3d 1351, 1357-58, 90 USPQ2d 1417, 1422 (Fed. Cir. 2009) (as quoted in Par Pharm., Inc. v Twi Pharm., Inc., 773 F.3d 1186, 112 USPQ2d 1945, 1952 (Fed. Cir. 2014).
Therefore claims 3-4 are obvious.
Malvar & Gilmer teaches host cells in the title and claims 12 and 15 teach, for example, transgenic cotton so claims 5, 6, 7, and 8 are obvious. Its claim 16 teaches a seed and so claim 9, 10, and 11 are obvious; as well as is claim 14 a method for producing the seed. At the bottom of column 9 Malvar & Gilmer teaches adding additional Cry proteins and thus claims 12 and 13 are obvious. Since claim 16 is anticipated by Malvar & Gilmer, it is also obvious.
Cry1Aa-like protein [Bacillus thuringiensis]
Sequence ID: AIW52617.1Length: 1180Number of Matches: 1
Related Information
AlphaFold Structure-3D structure displays
Range 1: 132 to 459GenPeptGraphicsNext MatchPrevious Match
Alignment statistics for match #1
Score Expect Method Identities Positives Gaps
664 bits(1713) 0.0 Compositional matrix adjust. 320/328(98%) 324/328(98%) 0/328(0%)
Query 1 TQFTATETYISGRISVLKIQNFEVQLLSVFAQAANLHLSLLRDVVFFGQRWGFSTTTVNN 60
TQFTATETYISGRISVLKIQNFEVQLLSVFAQAANLHLSLLRDVVFFGQRWG STTTVNN
Sbjct 132 TQFTATETYISGRISVLKIQNFEVQLLSVFAQAANLHLSLLRDVVFFGQRWGVSTTTVNN 191
Query 61 YYNDLTEEISTYTDYAVRWYNTGLERVWGPDSRDWVRYNQFRRELTLTVLDIVALFPNYD 120
YYNDLTEEISTYTDYAVRWYNTGLERVWGPDSRDWVRYNQFRRELTLTVLDIV+LFPNYD
Sbjct 192 YYNDLTEEISTYTDYAVRWYNTGLERVWGPDSRDWVRYNQFRRELTLTVLDIVSLFPNYD 251
Query 121 SRRYPIRTVSQLTREIYTNPVLENFDGSFRGMAQRIEQNIRQPHLMDILNSITIYTDVHR 180
SRRYPIRTVSQLTREIYTNPVLENFDGSFRGMAQRIEQNIRQPHLMDILN+ITIYTDVHR
Sbjct 252 SRRYPIRTVSQLTREIYTNPVLENFDGSFRGMAQRIEQNIRQPHLMDILNTITIYTDVHR 311
Query 181 GFNYWSGHQITASPVGFSGPEFAFPLFGNAGNAAPPVLVSLTGLGIFRTLSSPLYRRIIL 240
GFNYWSGHQITASPVGFSGPEF FPLFGNAGNAAPPVLVSLTGLGIFRTLSSP YRRIIL
Sbjct 312 GFNYWSGHQITASPVGFSGPEFTFPLFGNAGNAAPPVLVSLTGLGIFRTLSSPFYRRIIL 371
Query 241 GSGPNNQELFVLDGTEFSFASLTTNLPSTIYRQRGTVDSLDVIPPQDNSVPPRAGFSHRL 300
GSGPNNQELFVLDGTEFSFASLTTN+PSTIYRQRGTVDSLD+IPPQDNSVP RAGFSHRL
Sbjct 372 GSGPNNQELFVLDGTEFSFASLTTNIPSTIYRQRGTVDSLDLIPPQDNSVPARAGFSHRL 431
Query 301 SHVTMLSQAAGAVYTLRAPTFSWQHRSA 328
SHVTMLSQAAGAVYTLRAPTFSWQHRSA
Sbjct 432 SHVTMLSQAAGAVYTLRAPTFSWQHRSA 459
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (2014) AIW52617 in view of Malvar & Gilmer ("MaG"), US 7,250,501 B2, issued 31 July 2007 as applied to claim 8 above, and further in view Lira et al., US Patent No. 8,697,642 B2, issued 15 April 2014.
As seen above, claim 8 is obvious but Malvar & Gilmer does not teach combining its claimed toxin with a different event in a transgenic plant line. Lira et al. however teaches the use of combining one Cry toxin with other Cry toxins, such as Cry3Bb1 (MON88017) and thus claim 15 is obvious. Lira et al., col. 2.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). MPEP § 804.
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-16 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 12-15 of copending Application No. 16/376,169 (‘169 Application). Although the conflicting claims are not identical, they are not patentably distinct from each other.
The following examined U.S. Patent applications are members of the patent application family; all issued as patents. All are Continuation applications (not divisionals).
First, the 15/868,676; now U.S. Patent No. 10,703,782 where the claims (1-14) focus on SEQ ID NO:6 and SEQ ID NO:12. Both identified as chimeric toxins. Spec. pp. 11-12; and para. 0038. The initial claims were at least approximately the same as the instant claims.
Second, 16/894,459; now U.S. Patent No. 11,702,455 B2 where the claims (1-17) focus on SEQ ID NO:8. The initial claims were at least approximately the same as the instant claims.
Third, 18/319,022; now U.S. Patent No. 12,240,874; where the claims (1-19) focus on SEQ ID NO:4 which is a chimeric protein. Spec., para. 0030. The initial claims were the at least approximately the same although they were immediately replaced by amended claims.
Thus the currently pending claims are genus claims reading on the species in the issued patents but they are species that are called out by the instant application and claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUSSELL T BOGGS whose telephone number is (571)272-2805. The examiner can normally be reached Monday - Friday, 0800 to 1830 Mtn.
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/RUSSELL T BOGGS/ Ph.D., J.D. Examiner, Art Unit 1663
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